The present invention is directed to the dihydrobromide salt of 2-guanidino-4-(2-methyl-4-imidazolyl)thiazole, and to a one-pot, high yield process for its preparation from 2-methyl-4(or 5)-acetylimidazole, a compound having essentially equivalent tautomeric forms: ##STR1## previously named 1-(2-methyl-4-imidazolyl)ethanone.
2-Guanidino-4-(2-methyl-4-imidazolyl)thiazole (or a pharmaceutically-acceptable salt thereof) is a highly potent histamine H.sub.2 antagonist useful in the treatment of gastric hyperacidity and peptic ulcers (LaMattina and Lipinski, U.S. Pat. No. 4,374,843).
Heretofor, 2-guanidino-4-(2-methyl-4-imidazolyl)thiazole has been generally disclosed in the form of pharmaceutically-acceptable salts (which would encompass the present dihydrobromide salt), but has been specifically described as its monohydrobromide salt (LaMattina and Lipinski, cited above), generally isolated in amorphous form. The form of 2-guanidino-4-(2-methyl-4-imidazolyl)thiazole presently employed clinically is the dihydrochloride salt, prepared from the present crystalline dihydrobromide salt via the free base. Heretofor, 2-guanidino-4-(2-methyl-4-imidazolyl)thiazole was prepared (as said monohydrobromide salt) from 2-methyl-5-acetylimidazole in separate bromination and cyclization steps in an over-all yield of 40% (reflecting step yields of 51% and 79%).